Edaravone, an ROS scavenger, ameliorates photoreceptor cell death after experimental retinal detachment

Mi In Roh, Yusuke Murakami, Aristomenis Thanos, Demetrios G. Vavvas, Joan W. Miller

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Purpose. To investigate whether edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one), a free radical scavenger, would be neuroprotective against photoreceptor cell death in a rat model of retinal detachment (RD). Methods. RD was induced in adult Brown Norway rats by subretinal injection of sodium hyaluronate. Edaravone (3, 5, or 10 mg/kg) or physiologic saline was administered intraperitoneally once a day until death on day 3 or 5. Oxidative stress in the retina was assessed by 4-hydroxynonenal staining or ELISA for protein carbonyl content. Photoreceptor death was assessed by TUNEL and measurement of the outer nuclear layer thickness. Western blot analysis and caspase activity assays were performed. Inflammatory cytokine secretion and inflammatory cell infiltration were evaluated by ELISA and immunostaining, respectively. Results. RD resulted in increased generation of ROS. Treatment with 5 mg/kg edaravone significantly reduced the ROS level, along with a decrease in TUNEL-positive cells in the photoreceptor layer. A caspase assay also confirmed decreased activation of caspase-3, -8, and -9 in RD treated with edaravone. The level of the antiapoptotic Bcl-2 was increased in detached retinas after edaravone treatment, whereas the levels of the stress-activated p-ERK1/2 were decreased. In addition, edaravone treatment resulted in a significant decrease in the levels of TNF-α, MCP-1, and macrophage infiltration. Conclusions. Oxidative stress plays an important role in photoreceptor cell death after RD. Edaravone treatment may aid in preventing photoreceptor cell death after RD by suppressing ROS-induced photoreceptor damage.

Original languageEnglish
Pages (from-to)3825-3831
Number of pages7
JournalInvestigative Ophthalmology and Visual Science
Volume52
Issue number6
DOIs
Publication statusPublished - May 1 2011
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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